A new dyslipidemia-based scoring model to predict transplant-free survival in patients with hepatitis E-triggered acute-on-chronic liver failure

Background/Aims Hepatitis E virus (HEV)-triggered acute-on-chronic liver failure (ACLF) has unacceptably high short-term mortality. However, it is unclear whether the existing predictive scoring models are applicable to evaluate the prognosis of HEV-triggered ACLF. Methods We screened datasets of patients with HEV-triggered ACLF from a regional tertiary hospital for infectious diseases in Shanghai, China, between January 2011 and January 2021. Clinical and laboratory parameters were recorded and compared to determine a variety of short-term mortality risk factors, which were used to develop and validate a new prognostic scoring model. Results Out of 4952 HEV-infected patients, 817 patients with underlying chronic liver disease were enrolled in this study. Among these, 371 patients with HEV-triggered ACLF were identified and allocated to the training set (n = 254) and test set (n = 117). The analysis revealed that hepatic encephalopathy (HE), ascites, triacylglycerol and apolipoprotein A (apoA) were associated with 90-day mortality (P < 0.05). Based on these significant indicators, we designed and calculated a new prognostic score = 0.632 × (ascites: no, 1 point; mild to moderate, 2 points; severe, 3 points) + 0.865 × (HE: no, 1 point; grade 1–2, 2 points; grade 3–4, 3 points) − 0.413 × triacylglycerol (mmol/L) − 2.171 × apoA (g/L). Compared to four well-known prognostic models (MELD score, CTP score, CLIF-C OFs and CLIF-C ACLFs), the new scoring model is more accurate, with the highest auROCs of 0.878 and 0.896, respectively, to predict 28- and 90-day transplantation-free survival from HEV-triggered ACLF. When our model was compared to COSSH ACLF IIs, there was no significant difference. The test data also demonstrated good concordance. Conclusions This study is one of the first to address the correlation between hepatitis E and serum lipids and provides a new simple and efficient prognostic scoring model for HEV-triggered ACLF. Supplementary Information The online version contains supplementary material available at 10.1186/s12944-023-01826-y.


Supplementary File 1
The inclusion of and exclusion criteria for HEV-triggered ACLF.

Supplementary File 2
Laboratory detection and instruments used in this study.

Supplementary File 3
Diagnosis of HEV infection, liver cirrhosis, and ACLF.

Supplementary File 4
Definition and range of underlying chronic liver diseases. Table 1 The number and prevalence of organ failure in patients with HEV-triggered ACLF upon admission.

Table 2
Baseline characteristics and outcome of patients with HEV-triggered ACLF in the training and test cohorts. Table 3 Risk factors associated with 90-day mortality in patients with CHB etiology. Table 4 Risk factors associated with 90-day mortality in patients with fatty liver disease etiology. Table 5 Risk factors associated with 90-day mortality in patients from the training cohort using a multivariate Cox PH Model. Figure 1 Serum lipid levels between patients with or without bacterial infection among HEV-triggered ACLFs at the time of study enrollment.

Figure 2
Baseline serum lipid levels in HEV-triggered ACLFs with no, one, two or ≥ three organ failures.

Supplementary File 1
The inclusion of and exclusion criteria for HEV-triggered ACLF.
4952 patients infected with HEV were initially identified. A total of 3427 cases were then excluded for several reasons: 2843 outpatients, 222 pregnancy women, 118 for lack of medical records, 66 for HIV co-infections, 87 for having tuberculosis, 10 for coexistence of other viral infection markers ( including 5 anti-HBc IgM+ individuals, 3 HAV IgM+ individuals, 1 CMV IgM+ individual and 1 CMV/EBV IgM+ individual.) and 19 duplicate cases. Furthermore, patients who received lipid-lowering therapy (n=62) were also excluded from initial screening. Seven patients received liver transplantation within 90 days of the diagnosis of ACLF and were excluded; the remaining 817 patients were therefore included in the final analysis.

Supplementary File 2 Laboratory detection and instruments used in this study.
In this study, anti-HEV immunoglobulin M (IgM) and G (IgG) level were tested using enzyme-linked immunosorbent assay (ELISA) (MP Biomedicals, Singapore). Liver function and serum lipids were examined by an automated biochemistry-analysis instrument (7600 Series; Hitachi, Japan). Coagulation indicators were measured by an automatic coagulometer (STA-R; Diagnostica Stago, Asnieres-sur-Seine, France), and the international normalized ratio (INR) was calculated as well. Serum HBV markers were detected using ELISA (ARCHITECT i2000 SR; Abbott, Germany). HBV DNA quantification was detected using real-time PCR (ABI 7500; Applied Biosystems Inc, United States).

Diagnosis of HEV infection, liver cirrhosis, and ACLF.
HEV infection was diagnosed by two consecutive positive serum anti-HEV immunoglobulin M (IgM) test and by seroconversion to positive HEV immunoglobulin G during follow-up recorded in the hospital clinical database.
Liver cirrhosis was defined histologically as a form of distortion of the hepatic architecture and regenerative nodule, which was confirmed by radiological or histological evidence 1 .